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Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015.

ABSTRACT: The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several "superspreading" events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.

SUBMITTER: Kim YS

PROVIDER: S-EPMC6537729 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015.

Kim Yeon-Sook YS Aigerim Abdimadiyeva A Park Uni U Kim Yuri Y Rhee Ji-Young JY Choi Jae-Phil JP Park Wan Beom WB Park Sang Won SW Kim Yeonjae Y Lim Dong-Gyun DG Inn Kyung-Soo KS Hwang Eung-Soo ES Choi Myung-Sik MS Shin Hyoung-Shik HS Cho Nam-Hyuk NH

Emerging infectious diseases 20190617 6

The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several "superspreading" events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic ...[more]

PMID: 30900977

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Project description:BackgroundEpidemiologic parameters are important in planning infection control policies during the outbreak of emerging infections. Korea experienced an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection in 2015, which was characterized by superspreading events in healthcare settings. We aimed to estimate the epidemiologic parameters over time during the outbreak to assess the effectiveness of countermeasures.Materials and methodsPublicly available data pertaining to the MERS outbreak in Korea were collected. We estimated the incubation periods of 162 cases whose sources of exposure were identified and the temporal trend was evaluated. Factors influencing incubation duration were analyzed. The generational reproduction number (Rg ) and case reproduction number (R(c) ) were estimated over time.ResultsThe estimated median incubation period was 7.4 days (95% CI, 6.9-8.0). Median incubation periods tended to be longer over time as the disease generation progressed: 6.16 days (95% CI, 5.38-6.97), 7.68 days (95% CI, 7.04-8.44), and 7.95 days (95% CI, 6.25-9.88) in the first, second, and third generations, respectively. The number of days of illness in the source cases at the time of exposure inversely correlated with the incubation periods in the receiving cases (HR 0.91 [95% CI, 0.84-0.99] per one illness day increase; P=0.026). This relationship was consistent (HR 0.83 [95% CI, 0.74-0.93] per one illness day increase) in the multivariable analysis incorporating clinical characteristics, the order of generation, and a link to superspreaders. Because the third generation cases were exposed to their source cases in the early stage (median one day) compared to the second generation cases (median 6 days), the temporal trend of incubation periods appears to be influenced by early isolation of symptomatic cases and reduction of potential exposure to source cases in the later stage. Rg declined rapidly from 28 to 0.23 in two generations. R(c) dropped below the epidemic threshold at one on May 31, 2015, which approximately coincided with the initiation of the stringent countermeasures.ConclusionsDespite the initial delay, the stringent countermeasures targeted towards second generation cases appeared to effectively contain the MERS outbreak in Korea as suggested by the decline of R(c) shortly after implementation. Except for superspreading events, the transmission potential for MERS-CoV seems to be low. Further research should be focused on characterizing superspreaders in comparison to non-transmitting cases with regard to environmental, behavioral, and virologic and host genetic factors in order to better prepare for future outbreaks of MERS-CoV.

Dataset Information

Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015.

Publications

Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015.

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